Gastrointestinal Mantle Cell Lymphoma Research Articles

Clinical and endoscopic characteristics of gastrointestinal mantle cell lymphoma

Objective: To study the clinical and endoscopic features of mantle cell lymphoma (MCL). Methods: The clinical data and endoscopic characteristics of 20 patients with gastrointestinal MCL treated in the Affiliated Hospital of Zunyi Medical University and the Digestive Endoscopy Center of Guizhou Medical University from January 2011 to January 2021 were collected, and the histological and immunohistochemical characteristics of the tumor were observed. Meanwhile, 44 cases of non-gastrointestinal MCL in the above two hospitals in the same period were also enrolled. The clinical and endoscopic differences between the two groups were compared. Results: Among the 20 patients with gastrointestinal MCL, the male to female ratio was 4∶1 (16/4), the average age was (60.3±9.7) years, and 11 patients (55.0%, 11/20) were over 60 years old. The main clinical manifestations of 20 patients at the onset of the disease were bloody stool or black stool in 9 cases (45.0%), abdominal pain in 8 cases (40.0%). Moreover, 5.0% (1/20) had B symptoms (fever, night sweat and weight loss). The most frequently involved site was colorectum (50.0%). Endoscopic findings showed mucosal polypoid lesions in 13 cases (65.0%, 13/20), involving multiple intestinal segments, with polyp diameter of 0.2-3.5 cm. Two cases (10%) were in stage Ⅲ and 18 cases (90%) were in stage Ⅳ according to Ann Arbor staging. Seven cases (35.0%, 7/20) had the involvement of the peritoneal and retroperitoneal lymph nodes, 9 cases (45.0%, 9/20) had the involvement of the superficial lymph nodes in 45.0% (9/20), and 4 cases (20%, 4/20) had other extranodal invasion. Splenomegaly accounted for 35.0% (7/20). CD20, Bcl-2 and CD5 were positive or strongly positive in all gastrointestinal MCL tumor cells in 20 cases. Cyclin D1 was positive or strongly positive, accounting for 90.0% (18/20). The sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) was positive or strongly positive, accounting for 65.0% (13/20). The positive index of Ki-67 was 5%-80%. Twenty cases (100%, 20/20) were followed up. The median follow-up was 41.2 months (1-74 months). There was no significant difference in the 3-year overall survival rate between the gastrointestinal MCL patients (70.0%) and non-gastrointestinal MCL patients (72.7%) (χ2=0.051, P=0.822). Conclusions: Abdominal discomfort is the main symptom of gastrointestinal MCL, which often occurs in the colorectum and often presents with multiple polypoid lesions. There are relatively few cases with B symptoms and extranodal invasion, and the prognosis is not different from that of patients with non-gastrointestinal MCL.

S1763 Gastrointestinal Mantle Cell Lymphoma Discovered During Iron Deficiency Anemia Work-Up

S1763 Gastrointestinal Mantle Cell Lymphoma Discovered During Iron Deficiency Anemia Work-Up

A Unique Case of Mantle Cell Lymphoma Masquerading as a Cecal Mass

Mantle cell lymphoma (MCL), a type of B-cell non-Hodgkin's lymphoma, is a rare and aggressive disease with a poor prognosis due to its advanced presentation at diagnosis. It is characterized by a translocation in the Bcl-1 gene, which results in overexpression of cyclin D1. MCL is frequently seen in the form of multiple lymphomatous polyposis (MLP) in which innumerable polyps are observed in the gastrointestinal (GI) tract. In rare instances, MCL presents a single mass. The most common presentation involves male patients in their sixties, with generalized lymphadenopathy, extranodal involvement, and B symptoms (night sweats, fever, and weight loss). Endoscopic findings of MLP include cerebroid folding of the gastric mucosa and innumerable polyps extending from the duodenum to the large intestine and are reported in approximately 9% of all GI lymphomas. Less commonly, only 2–4% of GI malignancies present as a primary GI MCL as a single mass, usually in the stomach and ileocecal region in the intestine. Radiologic findings include lymphadenopathy, splenomegaly, multiple polyposis, or wall thickening with ulceration or mass formation. In most instances, advanced disease is found at diagnosis, for which 5-year survival ranges only from 26 to 46%, even when appropriate treatment is initiated. High mitotic rate, or Ki-67 index, is of prognostic value and is associated with poor prognosis. Treatment involves conventional chemo-immunotherapy consisting of R CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or RB (rituximab and bendamustine), with the latter being better tolerated and associated with longer progression-free survival. Surgical resection is usually limited to patients in which complications are seen such as bleeding, perforation, or bowel obstruction. We present a unique case of a 70-year-old male with nonbilious, nonbloody emesis, and symptomatic anemia who was found to have a cecal mass consistent with MCL.

Clinical characteristics and outcomes of primary versus secondary gastrointestinal mantle cell lymphoma

Primary gastrointestinal (GI) mantle cell lymphoma (MCL) is rare and the optimal management is unknown. We reviewed 800 newly diagnosed MCL cases and found 22 primary (2.8%) and 79 (9.9%) secondary GI MCL cases. Age, sex, and performance status were similar between primary and secondary cases. Secondary cases had more elevations in lactate dehydrogenase (28% vs 0%, P = 0.03) and a trend for a higher MCL international prognostic index (P = 0.07). Observation or local therapy was more common for primary GI MCL (29% vs 8%, P < 0.01), and autologous stem-cell transplant was more common for secondary GI MCL (35% vs 14%, P < 0.05). The median follow-up was 85 months. Primary and secondary GI MCL had similar 5-year progression-free survival (PFS) (30% vs 28%, P = 0.59) and overall survival (OS) (65% vs 66%, P = 0.83). The extent of GI involvement in primary GI MCL affected treatment selection but not outcome, with a 5-year PFS of 43% vs 14% vs 31% (P = 0.48) and OS of 57% vs 71% vs 69% (P = 0.54) in cases with single lesion vs multiple lesions in 1 organ vs multiple lesions in ≥2 organs. Less aggressive frontline treatment for primary GI MCL is reasonable. It is unknown whether more aggressive treatment can result in improved outcomes.

MCL-049: Clinical Characteristics and Outcomes of Primary Versus Secondary Gastrointestinal (GI) Mantle Cell Lymphoma (MCL)

Context: While GI involvement in nodal MCL (secondary GI MCL) is thought to be common, primary GI MCL without nodal or other extranodal involvement is rare. The optimal management of primary GI MCL is unclear. Objective: Compare the clinical characteristics and outcomes of primary vs secondary GI MCL. Design: Retrospective study. Setting: Tertiary academic center. Patients or other participants: Patients with newly diagnosed MCL with biopsy-proven GI involvement between 1/1990-2/2018 and seen at Mayo Clinic. Median follow-up was 85 months. Interventions: Management per treating physicians. Main outcome measures: Progression-free survival (PFS) and overall survival (OS). Results: Among 800 patients with newly diagnosed MCL, 22 (2.8%) had primary GI MCL and 79 (9.9%) had secondary GI MCL. Initial presentation of primary GI MCL included single lesion (mucosal, polyp, or mass; n=7), multiple lesions in 1 organ (n=7), and multiple lesions in ≥2 organs (n=8). Age, sex, and ECOG PS were similar between primary and secondary GI MCL. Secondary GI MCL had more LDH elevations (0 vs 20%, p=0.03) and a trend of higher MIPI score (p=0.07). Observation or local therapy were more common for primary GI MCL (29 vs 8%, p Conclusions: Primary and secondary GI MCL had similar outcomes albeit less aggressive treatment in primary cases. Extent of GI involvement in primary GI MCL did not affect outcome. Whether primary GI MCL should be treated the same as secondary GI MCL requires additional studies.

Correlative analysis of overall survival with clinical characteristics in 127 patients with mantle cell lymphoma: a multi-institutional cohort in Taiwan.

Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma often with extranodal involvement at diagnosis, and yet how this feature correlates with survival awaits elucidation. To address this issue, a correlative analysis between clinical features of 127 MCL patients and their overall survival (OS) was conducted. In this cohort, the median age at MCL diagnosis was 62years and 81% were males. Eighty-four percent of patients were Ann Arbor stage 4, and 15% were blastoid variants. In patients with gastrointestinal MCL, approximately 40% had gastric involvement. In treatment, CHOP-based induction chemotherapy was given to 61.1% of patients. One-third of patients undertook autologous stem cell transplant (SCT), and 4.7% had allogeneic SCT. The median OS was 82months and well-stratified in MIPI risk groups. In the multivariate analysis for OS, blastoid variants and gastric involvement were both independent risk factors whereas auto-SCT had a protective effect. Overall, this study corroborated with the current understandings and international therapeutic standards for MCL. Auto-SCT associated with a better OS while allo-SCT remained an option for blastoid variants and those whofailed Auto-SCT. Interestingly, patients with gastric involvement tended to have worse survival, a finding that spawns more studies to investigate the mechanism.

Clinicopathologic features and prognosis of gastrointestinal mantle cell lymphoma

Objective: To investigate the clinicopathologic features and prognosis of gastrointestinal mantle cell lymphoma (GI-MCL). Methods: Clinical data of 38 GI-MCL patients diagnosed at Beijing Friendship Hospital from January 2002 to January 2016 were retrospectively reviewed morphologically and immunophenotypically. IgH/CCND1 gene fusion was assessed by fluorescent in situ hybridization (FISH). For comparison, 60 cases of non-GI-MCL were randomly selected to extract the differences inclinicopathological features and patient survival between the two groups. Results: Of 38 patients with GI-MCL, the median age was 62 years (range: 35-78 years, 23 males and 15 females), of which patients of 60 years of age or older accounted for 55.3%. Patients with clinical course of less than 6 months accounted for 81.1%(30/37). The main symptoms included abdominal pain, diarrhea, anorexia and hematochezia. Those with B symptoms accounted for 32.4%(12/37). The tumor most often involved lleocecal region (57.9%, 22/38), followed by rectum (36.8%, 14/38) and sigmoid colon (28.9%, 11/37), and the stomach accounted for 18.4%(14/38). Endoscopic polypoid lesions were found in 33 cases (86.8%, 33/38), of which 22 cases (66.7%, 22/33) were multiple. Five cases (13.2%, 5/38) presented with local protuberant neoplasm. According to Ann Arbor staging, 3 cases (7.9%, 3/38) were at stage Ⅰ, 4 cases (10.5%, 4/38) were at stage Ⅱ, and 31 cases (81.6%, 31/38) were at stage Ⅳ. The number of patients with tumor involvement of abdominal and retroperitoneal lymph nodes accounted for 45.7%(16/35), including 41.7%(15/36) involving the superficial lymph node, 17.1%(6/35) involving extranodal sites, and 23.5%(8/34) having splenomegaly. All of the 38 cases were classic MCL, and the tumor was composed of uniform lymphoid cells and effacing normal mucosal structure. All tumors were positive for CD20 and CD5. 97.4% (37/38) tumors were positive for cyclin D1, and 92.0% (23/25) tumors were positive for SOX11. FISH test was positive in 1 case of cyclin D1 negative tumor. Twenty-eight patients (73.7%) had a median follow-up of 25.0 months (range: 3-79 months). The 3-year survival rate for stage Ⅰ-Ⅱ and stage Ⅲ-Ⅳ of patients were 80.0% and 69.1%, respectively (P> 0.05). The 3-year survival rate for GI-MCL and non-GI-MCL patients were 71.7% and 72.5%, respectively (P>0.05). Single factor analysis showed that age of >60 years and splenomegaly were correlated with a worse overall survival rate (P<0.05). Conclusions: Gastrointestinal malaise is the most common presenting symptom in GI-MCL patients. GI-MCL more commonly involves colorectum with more frequent multiple polypoid lesions. Patients of age >60 years and with splenomegaly have poor prognosis. There is no difference in the prognosis between GI-MCL and non-GI-MCL patients.

Looks Can Be Deceiving: An Atypical Presentation of Mantle Cell Lymphoma

Introduction: Primary gastrointestinal(GI) mantle cell lymphoma (MCL) is a rare and aggressive malignancy. Endoscopy typically shows multiple lymphomatous polyposis (MLP) but other findings have been reported. We describe a case of primary GI MCL diagnosed during routine colon cancer screening. Case: A 61-year-old Hispanic female presented for a routine colonoscopy. Fifteen years prior, she underwent colonoscopy with polypectomy in El Salvador; report was not available. She denied fevers, chills, weight loss, diaphoresis, abdominal pain, melena, and hematochezia. Abdominal exam was benign and without lymphadenopathy. On colonoscopy, 3 sigmoidal polyps- all less than 5mm- were resected; the remaining mucosa was normal in appearance. Histology for 2 of the polyps showed lymphoid infiltrate with CD20+ B cells, reactive germinal centers, and expanded mantle zones, consistent with mantle cell lymphoma. The third polyp was an adenoma. Patient was referred to oncology and a workup of CT scans, FDG-PET CT, bone marrow biopsy and flow cytometry were normal. Patient declined chemotherapy and was observed. A colonoscopy 3 months later showed normal-appearing mucosa but biopsies from each colonic segment demonstrated diffuse MCL. Discussion: Primary GI MCL accounts for 1-4% of all GI lymphomas. The most common endoscopic finding is intestinal MLP but previous cases report ulcerated lesions, mucosal color changes or thickening, and frank masses. Our patient only had 3 small polyps on the initial screening and normal-appearing mucosa on the repeat endoscopy. Microscopic evidence of MCL is actually seen in two-thirds of cases with endoscopically normal mucosa but the significance of this on patient outcome is unclear. Primary GI MCL is often diagnosed in end stages and has a poor prognosis but the median survival remains to be studied. Chemotherapy regimens such as CHOP achieved high remission rates but for short time periods. More recently, the hyper-CVAD/MA regimen with rituximab has been established as an effective cytoreductive regimen with a high response rate. Our patient was offered bendamustine and rituximab, an effective regimen often utilized in older MCL patients. Specific regimens vary based on disease severity and patient's functional status. This case highlights an atypical presentation of a rare malignancy, the importance of timely screening colonoscopies, and the consideration of performing random colon biopsies on patients with MCL polyp pathology.

Primary Gastrointestinal Mantle Cell Lymphoma Involving Colon and Gallbladder: A Case Report

Primary Gastrointestinal Mantle Cell Lymphoma Involving Colon and Gallbladder: A Case Report

A Single Mass Forming Colonic Primary Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin's lymphoma (NHL) comprising around 7% of adult NHL. It is characterized by a chromosomal translocation t(11:14) and overexpression of Cyclin D1. The incidence of secondary gastrointestinal tract involvement in MCL ranges from 10 to 28% in various series. However primary gastrointestinal MCL is very rare, accounting for only 1 to 4% of primary gastrointestinal lymphomas. The most common endoscopic feature of primary intestinal MCL is multiple lymphomatous polyposis. In rare cases it presents as protruded lesions or superficial lesions. Single colonic mass presentation is an extremely infrequent presentation. MCL has an aggressive course with quick progression, and most cases are discovered in the advanced stages. Colonic biopsies with histologic examination and specific immunohistochemical staining are the gold standard for a proper diagnosis. We report a case of a single mass forming mantle cell lymphoma of the ascending colon in a 57-year-old female patient with unusual colonoscopic and radiologic features and describe the therapy the patient received, thereby adding to the spectrum of clinical presentations of this aggressive lymphoproliferative disorder.

Primary gastrointestinal mantle cell lymphoma: a retrospective study.

Primary gastrointestinal tract mantle cell lymphoma is very rare. There is paucity of literature regarding natural history and outcome of this unusual entity. The aim of the present study was to analyze clinical profile, epidemiological parameters, and outcome of primary gastrointestinal mantle cell lymphoma patients treated at our institute. This was a retrospective observational study of consecutive patients diagnosed with primary gastrointestinal mantle cell lymphoma at our institute between 2001 and 2012. A total of seven patients, all males with a median age of 67.7years, were diagnosed with primary gastrointestinal mantle cell lymphoma. Sites involved were the stomach, colon, and rectum. Blastoid and diffuse variants were observed in three patients each, and one patient had nodular pattern. Five patients received cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy. Only one patient achieved complete remission and remained disease free for 21months before being lost to follow up. The remaining four patients had inadequate response to CHOP chemotherapy with a median survival of 6months. Cyclophosphamide, vincristine, prednisolone (CVP) was given to one patient in view of poor performance status. He had progressive disease and died after first cycle of chemotherapy. One patient is currently undergoing treatment and receiving rituximab with chemotherapy. Primary gastrointestinal mantle cell lymphoma is highly aggressive with the Mantle Cell Lymphoma International Prognostic Index (MIPI) scores in high-risk group; survival is poor compared to nodal mantle cell lymphoma involving the gastrointestinal tract; patients respond poorly to CHOP chemotherapy. As majority of patients are elderly and not eligible for transplant, the use of rituximab in remission induction and maintenance should be considered to improve outcome of these patients.

Gastrointestinal Mantle Cell Lymphoma: incidental finding on routine CT scan following pneumothorax.

Gastric mantle cell lymphoma is a rare form of gastrointestinal tumor and represents 2.5–7% of all non-Hodgkin’s lymphomas. A 69-year-old maleadmitted with spontaneous pneumothorax was found to have a gastric masson CT scan. Results of histopathological,immunohistochemical and genetic analysis were consistent with mantle cell lymphoma(MCL).Patient responded well to intensive chemotherapy and subsequent allogeneic hematopoietic stem cell transplant and remains in complete remission.We would like to emphasize that a gastric mass, as in this case can occur as a rare presentation of MCL involving the gastrointestinal tract without any other overt signs and symptoms. Journal of Advances in Internal Medicine 2013;02(01):24-26 DOI: http://dx.doi.org/10.3126/jaim.v2i1.7635

An Unexpected Case of Metachronous Diffuse Gastrointestinal Mantle Cell Lymphoma and Aggressive Metastatic Colonic Adenocarcinoma

Purpose: A 70-year-old woman was evaluated for hematochezia. Past history included hypertension. Physical examination was normal. Colonoscopy revealed pancolonic multiple erythematous polypoid lesions. Upper endoscopy showed nodular gastroduodenal mucosa. Diffuse gastrointestinal (GI) mantle cell lymphoma (MCL) was confirmed with histopathological and immunohistochemical studies. Staging PET/CT scan showed increased FDG uptake in gastric fundus and colon but no nodal involvement, suggesting primary GI MCL. Peripheral blood smear and bone marrow aspirate were normal. Combination chemotherapy consisted of 6 cycles R-CHOP regimen and maintenance rituxan. Endoscopy and PET/CT at 6 months confirmed successful response. Surveillance PET/CT at 12 months showed abnormality in the cecum. Colonoscopy revealed single 3 cm friable ulcerated cecal lesion suspicious for recurrence of MCL. Biopsy showed poorly differentiated adenocarcinoma. Right hemicolectomy revealed T4N2M0 with recurrence of MCL in appendix. After slow post-operative recovery, a restaging PET/CT was done prior to adjuvant chemotherapy. Multiple new hepatic lesions were confirmed as colon cancer metastases. After discussing treatment options, patient opted for hospice care. While colorectal cancer is a common GI malignancy, primary GI lymphoma is not. MCL often invades the GI tract but primary GI MCL is rare. Most frequent endoscopic finding of MCL is multiple lymphomatous polyposis, a rare entity accounting for 2% of primary GI lymphomas. MCL is a moderately aggressive disease. Median survival is 3 years. Most patients have advanced disease at diagnosis. 50% have bone marrow infiltration, 25% have involvement of GI tract. Leukemic transformation occurs in 25%. Tumor cells express pan-B-cell markers and the T-cell marker CD5. Overexpression of cyclin D1 has been noted. Combined chemotherapy, chemo-immunotherapy, peripheral stem cell transplantation are treatments of choice. Concomitant GI tract metachronous malignant lymphoma and adenocarcinoma are rare. Less than ten cases of synchronous GI MCL and colon cancer have been reported in literature. To our knowledge there has been no report of diffuse primary GI MCL with metachronous aggressive colon cancer detected incidentally. Further investigation of a potential relationship between MCL and colon cancer is warranted. Recognizing a relationship may help with accurate management and surveillance. Definitive studies are required to expand our findings and study the genetic basis of these observations.

Synchronous primary gastric mantle cell lymphoma and early gastric carcinoma: A case report

Mantle cell lymphoma (MCL) commonly invades the gastrointestinal (GI) tract. However, primary GI MCL is rare. We experienced a case of synchronous early gastric cancer (EGC) with primary gastric MCL found as a single early lesion rather than as multiple lymphomatous polyposis. An EGC was found in the cardia of a 64-year-old male on a routine GI endoscopic examination. A specimen obtained by total gastrectomy revealed another slightly elevated lesion in the pylorus. Microscopically, monotonous small- to medium-sized atypical lymphocytes with angulated nuclei formed a mass beneath the gastric mucosa. On immunohistochemical staining, the tumor cells revealed strong positivity for cyclin D1, positivity for both CD20 and bcl-2, and weak positivity for CD5, suggesting MCL. Clinically, there was no lymphoma in any other part of the body. This is the first case of an EGC accompanying a primary gastric MCL. Further investigation of a relationship between MCL and EGC and of factors that may affect GI involvement of MCL is necessary.

Safety and Antitumor Efficacy of the Proteasome Inhibitor Carfilzomib (PR-171) Dosed for Five Consecutive Days in Hematologic Malignancies: Phase 1 Results.

Introduction: Carfilzomib (CFZ) is a structurally- and mechanistically-novel proteasome inhibitor (PI) of the peptide epoxyketone class that exhibits a high level of selectivity for the unique N-terminal threonine active sites within the proteasome. CFZ is similar to bortezomib (BTZ; VELCADE®), in that it is a potent inhibitor of the chymotrypsin-like activity, but unlike BTZ, CFZ has shown minimal cross-reactivity with the other catalytic sites within the proteasome or across other protease classes. Preclinical human tumor xenograft models indicate that consecutive day (D1, D2) dosing resulting in 48 hours of proteasome suppression was superior to split dosing (D1, D4).Methods: This phase 1 sequential dose escalation trial tested an intensive proteasome inhibition schedule with CFZ administered as an intravenous push (IVP) daily (QD) for 5 consecutive days on a 14 day cycle. The doses administered ranged from 1.2 mg/m2 to 20 mg/m2. Multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) that included mantle cell lymphoma (MCL), Hodgkin's disease (HD), or Waldenström's macroglobulinemia (WM) were eligible if they had relapsed after 2 or more prior therapies.Results: A total of 29 subjects have been treated. The minimal effective dose (MED) was 11 mg/m2. A maximum of 80% proteasome inhibition was achieved in peripheral blood and mononuclear cells at ≥15 mg/m2. Five responses have occurred in 14 patients (6 MM, 3 MCL, 1 WM, 4 NHL) enrolled at ≥ the MED: 1 MM partial response (PR), 2 MM minimal responses (MR), 1 WM MR and one macroscopic CR in a patient with gastrointestinal MCL. Responses occurred in patients whose disease had failed therapy with BTZ, immunomodulatory agents, and stem cell transplant. Four NHL patients have had stable disease and remained on treatment for up to 7 months. Dose limiting toxicity reported at 20 mg/m2 included febrile neutropenia (reversible) and grade 4 thrombocytopenia. Grade 3 (25%) or grade 4 events (8%) were primarily hematologic events. Most withdrawals occurred due to the inconvenience of frequent visits, or progressive disease.Conclusions: This study demonstrates that intensive CFZ dosing leading to sustained proteasome inhibition is well tolerated. The selectivity of the epoxyketone class of PI may promote a favorable safety profile. Furthermore, antitumor responses in heavily pretreated patients suggest non-cross resistant activity. Phase 2 trials in MM and solid tumors are proceeding with an alternate IV schedule. An oral agent suitable for frequent dosing schedules is under development.

Preliminary results of a phase II study of low dose continuous chemotherapy for relapsed/refractory lymphoid malignancies

6732 Background: Low dose continuous (metronomic) chemotherapy has been shown to be effective in overcoming drug resistance and also exerting antiangiogenic activity. The aim of this study is to evaluate this approach in cases of relapsed/refractory lymphoid malignancies. Methods: Patients with ECOG-PS 0–2, and adequate bone marrow, hepatic and renal function who had relapsed/refractory disease after at least two chemotherapy regimens were eligible. Treatment consisted of: Etoposide 50 mg/day oral X 14 days; Chlorambucil 0.1 mg/kg/day oral X 14 days; Vincristine 2mg IV on days 1 and 14; Dexamethasone 200 mg IV on days 1 and 14; Rituxan (only in patients who had previously received less than 8 doses) 375 mg/m2 IV on days 1 and 14. Each cycle was repeated every 28 days. Results: From October 2003 to December 2004 total of 6 patients were enrolled (study is still ongoing at the time of submission). Age 23 - 70. Four male and two female. 5 patients were evaluable. 2/5 had major response: one with follicular lymphoma, significant response after 2 cycles; one with diffuse gastrointestinal mantle cell lymphoma, significant response after 3 cycles. 1/5 had minor response: nodular sclerosing Hodgkin’s lymphoma, responded after 2 cycles. 2/5 did not respond. Toxicity: Neutropenia: 1/5 grade 3, 1/5 grade 4; Thrombocytopenia: 1/5 grade 1; Neuropathy: 1/5 grade 2, 1/5 grade 3. Nausea: 2/5 grade 1, 1/5 grade 2. Conclusions: The preliminary results of this study indicate that metronomic administration of chemotherapy yields major and early response in some cases of relapsed/refractory lymphoid malignancies. No significant financial relationships to disclose.